Rescuing replication and osteogenesis of aged mesenchymal stem cells by exposure to a young extracellular matrix

Division of Research, Department of Comprehensive Dentistry, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900, USA.
The FASEB Journal (Impact Factor: 5.04). 04/2011; 25(5):1474-85. DOI: 10.1096/fj.10-161497
Source: PubMed


This study aimed to determine whether aging negatively affects MSC replication and osteogenesis and whether these features could be altered by exposure to an extracellular matrix (ECM) generated by marrow cells from young or old mice. A cell-free ECM was prepared from cultured femoral marrow cells from either 3- or 18-mo-old C57BL/6 mice (young-ECM or old-ECM, respectively). The replication and osteogenesis of young or old MSCs maintained on young-ECM vs. old-ECM as well as plastic were examined in vitro and in vivo. We found that the frequency of MSCs in marrow from old mice, measured by colony-forming cells, was only marginally lower than that of young mice. In contrast, defects in the self-renewal and bone formation capacity of old MSCs were remarkable. These defects were corrected by provision of a young-ECM but not old-ECM. In parallel cultures maintained on a young-ECM, the intracellular levels of reactive oxygen species from both old and young mice were reduced 30-50% compared to those maintained on old-ECM or plastic. We concluded that aging negatively affects the formation of an ECM that normally preserves MSC function, and aged MSCs can be rejuvenated by culture on a young-ECM.

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    • "The aging process itself has been associated with defective ECM production. For example, the reduced self-renewal and bone formation capacity of aged mesenchymal stem cells (MSCs) was corrected by culturing them on ECM from young MSCs (Sun et al. 2011). In analogy to that, proliferative defects of mouse adult fibroblasts harboring HGPS-linked Lmna mutation were rescued upon growth on ECM derived from wild-type cells (Hernandez et al. 2010). "
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    Genes & Development 02/2015; 29(3):225-237. DOI:10.1101/gad.255968.114 · 10.80 Impact Factor
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    • "In contrast, bone formation capacity of cells expanded on tissue culture plastic was dramatically diminished after 6e7 passages. Also, Sun et al. has shown that culturing freshly isolated human bone marrow mononuclear cells on stromal cell-derived extracellular matrix enhances the formation of colonies comprised of either osteoblast-like, fibroblast-like, or adiopcyte-like cells [10]. In addition, they also showed that culturing late-passage MSCs on fresh ECM recovered or at least retained the desired properties in these older cells. "
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    Biomaterials 02/2014; 35(13). DOI:10.1016/j.biomaterials.2014.01.081 · 8.56 Impact Factor
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    • "Studies in different tissues across species have clarified that the ECM constitutes an important part of progenitor cell niches [7,8]. While certain microenvironments in Drosophila, as expected, repress stem cell differentiation and promote adherence to the niche [8], even age-related differences in ECM composition directly influence stem cell function [32]. To begin understanding the remodeling events in the ECM microenvironment when HPCs are activated in a second tier of defense to liver injury, we used the AAF/PHx protocol to study transcriptional changes in ECM constituents during three phases of an HPC response, that is, the activation phase, the early proliferation and migration phase, and the late proliferation and migration phase. "
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    Fibrogenesis & Tissue Repair 12/2013; 6(1):21. DOI:10.1186/1755-1536-6-21
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